There are two objectives of this project: the first is to delineate, describe and analyze the major factors determining and/or regulating the cellular acid-base state of frog skeletal muscles so that the role of cells in the overall acid-base regulatory processes of the body can be better understood. The second objective is to develop a detailed, quantitative description of the permeation of bicarbonate and other anions through anion channels of the membrane under a variety of conditions and thereby deduce much detail about the essential molecular structures of the channel. These objectives are congenial because detailed knowledge of the determinants of HCO3- permeation is necessary for calculating passive bicarbonate fluxes and the counterbalancing active fluxes. The experimental approaches are much the same for both objectives: (1) Intracellular microelectrodes and similar techniques will be used to measure membrane conductance to anions as a function of external pH with cell pH kept constant and vice versa. This will be done for different temperatures, membrane voltages and external anion species. These experiments will give much detail about the intra- and extracellular factors which control anion permeability. (2) Radioactive anion tracer techniques will be used to investigate the effects of external and internal pH and external anion species on tracer anion fluxes. This research has clinically important implications: (1) The acid-base interactions between cells and extracellular fluid must be understood in order to make the diagnosis of acid-base disorders more precise. (2) The acid-base state of the cell interior is probably as important as that of extracellular fluid in determining overall body response to acid-base alterations. Hence, better diagnosis and treatment require knowledge of these processes.